title: Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.
abstract: Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.
authors.affiliation: Departamento de Química, Universidade Estadual de Maringá, Av. Colombo, 5790 CEP: 87020-900, Maringá, PR, Brazil.
authors.forename: Anelise S Nazari
authors.initials: AS
authors.lastname: Formagio
authors.forename: Lilian T Düsman
authors.initials: LT
authors.lastname: Tonin
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Foglio
authors.forename: Christiana
authors.initials: C
authors.lastname: Madjarof
authors.forename: João Ernesto
authors.initials: JE
authors.lastname: de Carvalho
authors.forename: Willian Ferreira
authors.initials: WF
authors.lastname: da Costa
authors.forename: Flávia P
authors.initials: FP
authors.lastname: Cardoso
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Sarragiotto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines